Abstract
In mammals, the permanence of hearing loss is due mostly to the incapacity of the cochlea to replace lost mechano-receptor cells (i.e., hair cells [HCs]). The generation of new HCs from a renewable source of progenitors is a principal requirement for developing a cell therapy within this sensory organ. A subset of stem cells, termed side population (SP), has been identified in several tissues of mammals. The ATP-binding cassette transporter Abcg2/Bcrp1 contributes to the specification of the SP phenotype and is proposed as a universal marker for stem/progenitor cells. A defining character of these SP cells is a high efflux capacity for Hoechst dye. Here, we demonstrate that Abcg2 transporter is expressed with two other stem/progenitor cell markers (i.e., Nestin and Musashi1) in distinct and overlapping domains of the supporting cells within the postnatal cochlea. We have developed and describe a fluorescence-activated cell sorting (FACS) technique that enables the purification of a discrete subpopulation of SP-supporting cells from the early postnatal mouse cochlea based on their ability to exclude Hoechst dye. These FACS-isolated cells can divide and express markers of stem/progenitor cells such as Abcg2, a determinant of the SP phenotype, and Musashi1, a neural stem/progenitor cell marker. These markers can differentiate cells expressing markers of HCs and supporting cells in vitro. Our observation that these SP cells are capable of differentiating into HC-like cells implies a possible use for such cells (i.e., the replacement of lost auditory HCs within damaged cochlea).
| Original language | English |
|---|---|
| Pages (from-to) | 332-339 |
| Number of pages | 8 |
| Journal | Stem Cells |
| Volume | 25 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2007 |
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Keywords
- Abcg2 transporter
- Hair cells
- Hearing loss
- Side population
- Side population-supporting cells
- Stem/progenitor cells
ASJC Scopus subject areas
- Cell Biology
Cite this
Distinct population of hair cell progenitors can be isolated from the postnatal mouse cochlea using side population analysis. / Savary, Etienne; Hugnot, Jean Philippe; Chassigneux, Yolaine; Travo, Cecile; Duperray, Christophe; Van De Water, Thomas R; Zine, Azel.
In: Stem Cells, Vol. 25, No. 2, 01.02.2007, p. 332-339.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distinct population of hair cell progenitors can be isolated from the postnatal mouse cochlea using side population analysis
AU - Savary, Etienne
AU - Hugnot, Jean Philippe
AU - Chassigneux, Yolaine
AU - Travo, Cecile
AU - Duperray, Christophe
AU - Van De Water, Thomas R
AU - Zine, Azel
PY - 2007/2/1
Y1 - 2007/2/1
N2 - In mammals, the permanence of hearing loss is due mostly to the incapacity of the cochlea to replace lost mechano-receptor cells (i.e., hair cells [HCs]). The generation of new HCs from a renewable source of progenitors is a principal requirement for developing a cell therapy within this sensory organ. A subset of stem cells, termed side population (SP), has been identified in several tissues of mammals. The ATP-binding cassette transporter Abcg2/Bcrp1 contributes to the specification of the SP phenotype and is proposed as a universal marker for stem/progenitor cells. A defining character of these SP cells is a high efflux capacity for Hoechst dye. Here, we demonstrate that Abcg2 transporter is expressed with two other stem/progenitor cell markers (i.e., Nestin and Musashi1) in distinct and overlapping domains of the supporting cells within the postnatal cochlea. We have developed and describe a fluorescence-activated cell sorting (FACS) technique that enables the purification of a discrete subpopulation of SP-supporting cells from the early postnatal mouse cochlea based on their ability to exclude Hoechst dye. These FACS-isolated cells can divide and express markers of stem/progenitor cells such as Abcg2, a determinant of the SP phenotype, and Musashi1, a neural stem/progenitor cell marker. These markers can differentiate cells expressing markers of HCs and supporting cells in vitro. Our observation that these SP cells are capable of differentiating into HC-like cells implies a possible use for such cells (i.e., the replacement of lost auditory HCs within damaged cochlea).
AB - In mammals, the permanence of hearing loss is due mostly to the incapacity of the cochlea to replace lost mechano-receptor cells (i.e., hair cells [HCs]). The generation of new HCs from a renewable source of progenitors is a principal requirement for developing a cell therapy within this sensory organ. A subset of stem cells, termed side population (SP), has been identified in several tissues of mammals. The ATP-binding cassette transporter Abcg2/Bcrp1 contributes to the specification of the SP phenotype and is proposed as a universal marker for stem/progenitor cells. A defining character of these SP cells is a high efflux capacity for Hoechst dye. Here, we demonstrate that Abcg2 transporter is expressed with two other stem/progenitor cell markers (i.e., Nestin and Musashi1) in distinct and overlapping domains of the supporting cells within the postnatal cochlea. We have developed and describe a fluorescence-activated cell sorting (FACS) technique that enables the purification of a discrete subpopulation of SP-supporting cells from the early postnatal mouse cochlea based on their ability to exclude Hoechst dye. These FACS-isolated cells can divide and express markers of stem/progenitor cells such as Abcg2, a determinant of the SP phenotype, and Musashi1, a neural stem/progenitor cell marker. These markers can differentiate cells expressing markers of HCs and supporting cells in vitro. Our observation that these SP cells are capable of differentiating into HC-like cells implies a possible use for such cells (i.e., the replacement of lost auditory HCs within damaged cochlea).
KW - Abcg2 transporter
KW - Hair cells
KW - Hearing loss
KW - Side population
KW - Side population-supporting cells
KW - Stem/progenitor cells
UR - http://www.scopus.com/inward/record.url?scp=33846917180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846917180&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2006-0303
DO - 10.1634/stemcells.2006-0303
M3 - Article
C2 - 17038670
AN - SCOPUS:33846917180
VL - 25
SP - 332
EP - 339
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 2
ER -